Single-cell genome and transcriptome sequencing methods have transformed many areas of biology and medicine. These methods enable scientists to identify biologically relevant differences between single cells in a population at higher resolution than previously possible. The goal of this proposal is to acquire funds for a Fluidigm C1 Single-Cell Auto Prep system that will enable the University of Rochester Genomics Research Center (GRC) to provide single-cell genome resources to our faculty and investigators. The GRC,, located within the James P. Wilmot Cancer Center (JPWCC) at the University of Rochester School of Medicine and Dentistry (SMD), is a shared resource laboratory whose mission is to provide high-throughput genome-level analysis to all University faculty and investigators. High-throughput sequencing resources in the GRC include an Illumina HiSeq2500 that was acquired through a 2013 NIH Shared Instrumentation Grant and an Illumina MiSeq that was purchased with internal University funds. The Fluidigm C1 Single-Cell Auto Prep system represents a significant advance in genome-wide analysis at single-cell resolution. Using the C1 Auto Prep in conjunction with existing GRC high-throughput sequencing resources, investigators on the University Main Campus (UR) and SMD will be able to explore several areas of interest, including: 1) determine gene expression profiles of phenotypically defined subpopulations of cells to give insight into heterogenetic responses, 2) investigate clonality and clonal evolution o various cancer types and 3) identify and monitor expression profiles unique to stem cells and their progeny. The Fluidigm instrument will primarily be used by a group of 5 Major and 5 Minor Users who are members of an existing strong Illumina user base with a diversity of NIH funded projects. Support provided by the GRC for high-throughput sequencing includes initial consultation on study design and rationale, sample preparation, library construction, sequencing and Bioinformatic data analysis. Computational support for the GRC is integrated with the Center for Integrated Research Computing (CIRC). These combined resources and support will allow experienced investigators as well as investigators unfamiliar with single-cell genomics to take immediate advantage of the Fluidigm system. Addition of Fluidigm technology as a cost effective shared resource will enable UR/SMD investigators to be at the forefront of cancer biology and stem cell research, provide a substantial benefit to multiple NIH funded projects and stimulate additional projects among new investigators, enabling them develop future NIH funded projects and compete at the highest scientific level.